tbuckley/cabot-search huggingface dataset:
Camrelizumab plus apatinib as induction therapy for locally advanced head and neck squamous cell carcinoma (IMplus): A single-arm phase II study.
Authors: Lulu Ye, Lin Zhang, Rongrong Li, Shengjin Dou, Wen Jiang, Guopei Zhu
Journal: Journal of Clinical Oncology (2022)

6060 Background: Immune checkpoint inhibitor combined with antiangiogenic agent has been investigated in many solid tumors, including advanced head and neck squamous cell carcinoma (HNSCC; NCT02501096), but the evidence is limited. This study was conducted to investigate the efficacy and safety of anti-programmed cell death-1 antibody camrelizumab plus antiangiogenic agent apatinib as induction therapy in patients with locally advanced HNSCC. Methods: In this single-center phase II trial (NCT04440917), patients with untreated locally advanced HNSCC who had inoperable lesions, could not tolerate surgery, or refused surgery were enrolled. Patients received camrelizumab 200 mg once every 2 weeks and apatinib 250 mg once daily for two 28-day cycles, followed by local treatment based on the re-examination results. The primary endpoint was objective response rate (ORR) after induction therapy, as assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. Simon’s two-stage design was adopted for this study. Results: Between December 2019 and July 2021, 18 patients were enrolled in the first stage. Eight (44%) patients had oropharyngeal carcinoma, nine (50%) had oral carcinoma, and one (6%) had hypopharyngeal carcinoma. There were six (33%), three (17%), and nine (50%) patients with stage III, IVA, and IVB disease, respectively. After induction therapy, six patients achieved complete response, nine achieved partial response, and three had stable disease, with an ORR of 83%. The study proceeded to the second stage and the enrollment for another 14 patients is ongoing. Two (11%) patients with partial response received surgery and adjuvant radiotherapy, and 16 (89%) received radical radiotherapy. With a median follow-up duration of 18 months (range, 9-26), only one disease recurrence and no deaths occurred. The most common adverse events during induction therapy were hypertension (ten [56%]), oral pain (nine [50%]), and increased aspartate aminotransferase (five [28%]). Only one [6%] grade 3 hypertension and one [6%] grade 3 proteinuria were observed, and no grade 4 or 5 adverse events occurred. Conclusions: Camrelizumab plus apatinib showed promising antitumor activity as induction therapy in patients with locally advanced HNSCC, with acceptable safety profile. Clinical trial information: NCT04440917.
Factors associated with adherence to remote patient monitoring for early detection of dehydration risk during radiation treatment for head and neck cancer.
Authors: Sarah Phillips, Eileen H. Shinn, Adam S. Garden, Beth Michelle Beadle, Maria Camero, George Baum, Sanjay Shete, Emilia Farcas, Kevin Patrick, Susan K. Peterson
Journal: Journal of Clinical Oncology (2022)

6076 Background: Remote patient monitoring (RPM) may improve the early detection and mitigation of cancer treatment-related complications, health-related outcomes and quality of life. RPM’s success may depend, in part, on patients’ adherence to remote monitoring protocols. However, factors that influence adherence to RPM are largely unknown. Daily blood pressure/pulse (BP/P), weight, and electronic patient-reported outcomes (ePROs) were monitored remotely in head and neck cancer (HNC) patients undergoing radiation treatment (RT) to identify dehydration risk. We evaluated potential factors associated with RPM adherence. Methods: During RT (average 6 to 7 weeks), participants were asked to take daily (Monday-Friday) measures of BP/P and weight using Bluetooth-enabled devices and to complete daily ePROs using a mobile tablet application (app). Data were provided to their physicians for daily review. The MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) was completed at baseline and end of RT, and 6-8 weeks post-RT completion. The Patient Activation Measure (PAM) was completed at baseline and 6-8 weeks post-RT completion. A device usability survey measuring perceived usefulness of RPM was completed at the end of RT. Adherence to daily monitoring was recorded objectively. Longitudinal analyses compared the relationship between demographic, clinical, and PRO data and monitoring adherence. Results: Participants (n = 169) were 80% male, 87% White, and 91% married. Overall adherence to monitoring BP/P, weight, and ePROs was 83%, 82% and 74%, respectively. Greater HN-specific symptom severity and interference was associated with decreased adherence to daily monitoring of BP/P, weight, and ePROs (P&lt; 0.021). Higher PAM scores were associated with higher adherence to daily monitoring of BP/P only (p = 0.006). Participants reported modest levels of perceived usefulness of RPM across four categories: symptom management, early problem detection, illness monitoring by healthcare provider, and feeling of security during RT. Only a single item indicating perceived feeling of security was associated with greater adherence to daily monitoring of blood pressure/pulse (p = 0.032) and weight (p = 0.007). Conclusions: A benefit of frequent RPM may be early detection and mitigation of symptoms during RT for HNC, however, increasing symptom burden experienced during treatment may interfere with adherence to daily monitoring. Better adherence may be attributed to patients perceiving a sense of security from daily monitoring and may suggest a potentially important value that patients gain from RPM. Understanding factors that impact patient adherence to RPM may help improve acceptability and clinical utility of RPM in oncology. Clinical trial information: NCT02253238.
Phase III randomized control study evaluating adjuvant metronomic chemotherapy in locally advanced head and neck cancers post-radical chemoradiation (MACE-CTRT).
Authors: Sunil Ramdhan Chopade, Vijay Maruti Patil, Vanita Noronha, Nandini Sharrel Menon, Atanu Bhattacharjee, Kavita Prakash Nawale, Shripad Dinanath Banavali, Kumar Prabhash, Vijayalakshmi Mathrudev
Journal: Journal of Clinical Oncology (2022)

6073 Background: Locally advanced head and neck cancer treated with radical chemoradiation have unsatisfactory outcomes. Oral metronomic chemotherapy improves outcomes in comparison to maximum tolerated dose chemotherapy in the palliative setting. There is also limited evidence that it may do so in an adjuvant setting. Hence this randomised study was conducted. Methods: Patients of HN cancer with primary in oropharynx, larynx or hypopharynx, with PS 0-2 post radical chemoradiation with documented complete response were 1:1 randomised to either observation or oral metronomic adjuvant chemotherapy (MAC) for 18 months. MAC consisted of weekly oral methotrexate (15 mg/m2) and celecoxib (200 mg PO BD). The primary endpoint was OS and the overall sample size was 1038. The study had 3 planned interim analyses for efficacy and futility. Results: 137 patients were recruited and an interim analysis was done. The 3 year PFS in the observation arm was 67.1% (95% CI 53.8-77.3) and the same in the MAC arm was 62.5%(95%CI 49.4-73.1). The corresponding hazard ratio was 1.402 (95% CI 0.7393-2.66, P-value = 0.3). The 3 year OS in the observation arm was 77.3% (95% CI 64.4-86) and the same in the MAC arm was 64.1% (95%CI 51-74.5). The corresponding hazard ratio was 1.588 (95% CI 0.8734-2.886, P-value = 0.1). Any grade mucositis was seen in 30 patients (45.5%) in the MAC arm and 20 patients (28.2%) in the observation arm (P-value = 0.05). The rate of grade 3 or above mucositis was 7.6%(n = 5) in the MAC arm and 1.4%(n = 1) in the observation arm (P-value = 0.106). Conclusions: Both arms had similar OS. Hence observation post complete response post radical chemoradiation remains the standard of care. Clinical trial information: CTRI/2016/09/007315.
A phase II study to evaluate the efficacy and safety of camrelizumab plus famitinib in advanced or metastatic thyroid cancer.
Authors: Dongmei Ji, Weina Shen, Muyu Kuang, Ying Liu, Huajun Li, Yu Wang, Qinghai Ji
Journal: Journal of Clinical Oncology (2022)

6085 Background: Many studies have confirmed that the combination with anti-vascular drugs can significantly improve the efficacy of anti-PD-1/PD-L1 inhibitor in a variety of tumors. Camrelizumab is a humanized anti-programmed cell death receptor 1 (PD-1) antibody. Famitinib is a tyrosine kinase inhibitor which exhibits anti-angiogenesis and antiproliferative effects via targeting VEGFR-2, c-Kit and PDGFR-β. Herein, we aimed to evaluate the efficacy and safety of camrelizumab plus famitinib in the treatment of advanced or metastatic thyroid cancer. Methods: A single-arm, open-label phase II study was conducted, patients (pts) with advanced or metastatic thyroid cancer were recruited, including radioiodine-refractory differentiated thyroid cancer (group 1), differentiated thyroid cancer ineligible for 131I treatment (group 2), medullary thyroid cancer (group 3) and anaplastic thyroid cancer (group 4). Pts received camrelizumab 200mg i.v. on day 1 of each 21-day cycle and oral famitinib 20mg po qd in 21-day cycles until progressive disease or drug intolerance. The primary endpoint was objective response rate (ORR). The secondary endpoints were safety, adverse events (AEs), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Results: Between Jan 14, 2020 and Feb 9, 2022, 74 pts were enrolled. There were 12/26/5/31 pts in group 1/2/3/4 respectively. Median follow-up time was 11.4 months. In group 1, of 12 evaluable pts, confirmed ORR, ORR and DCR accounted for 33.3%, 41.7% and 100.0%, respectively. In group 2, of 25 evaluable pts, the confirmed ORR and DCR were 44.0% and 96.0%, respectively. In group 3, of 5 evaluable pts, the confirmed ORR and DCR were 40.0% and 100.0%, respectively. In group 4, of 24 evaluable pts, the confirmed ORR, ORR and DCR were 62.5%, 75% and 95.8%, respectively. PFS and OS were not yet mature for group 1-3, and in group 4, of all enrolled pts, estimated median PFS was 8.4 months and estimated median OS was 13.6 months. 73 pts were included in safety set. The most common treatment related AEs were diarrhea (37.0%), palmoplantiplanar swelling syndrome (34.2%), hypertension (31.5%) and fatigue (31.5%). Conclusions: Camrelizumab plus famitinib demonstrated promising anti-tumor efficacy with acceptable toxicity in pts with advcanced or metastatic thyroid cancer. Clinical trial information: NCT04521348.
Impact on xerostomia for patients with nasopharyngeal carcinoma treated with superficial parotid lobe-sparing intensity-modulated radiation therapy (SPLS-IMRT): A prospective phase II randomized controlled study.
Authors: Huageng Huang, Jingjing Miao, Chong Zhao, Lin Wang
Journal: Journal of Clinical Oncology (2022)

6059 Background: In the intensity-modulated radiation therapy (IMRT) era, xerostomia remains one of the most common radiation-induced toxicities in nasopharyngeal carcinoma (NPC) patients. We first proposed the superficial parotid lobe–sparing IMRT (SPLS-IMRT) technique in NPC, which has been proved to significantly reduce the mean doses of bilateral entire parotid glands and superficial parotid lobes. To further validate its clinical benefits, we conducted a prospective phase II randomized controlled study to compare the incidence of xerostomia in NPC patients treated with SPLS-IMRT and conventional IMRT (C-IMRT). Methods: Patients with histologically confirmed NPC who met the eligibility criteria were randomly assigned in a 1:1 ratio to receive either SPLS-IMRT or C-IMRT. The V36 (the percentage volume receiving a dose of 36 Gy) of the entire parotid gland was constrained to be less than 40% in both groups. Additionally, V26 (the percentage volume receiving a dose of 26 Gy) of the superficial parotid lobe was constrained to be less than 30% in the SPLS-IMRT group. The primary endpoint was the incidence of xerostomia at 12 months post-IMRT. The secondary endpoints included the xerostomia questionnaire (XQ) score, unstimulated salivary flow rate (USFR), stimulated salivary flow rate (SSFR), and survival outcomes. Results: From January 2018 to September 2018, 90 patients were enrolled (45 per group). Eighty-two patients were included for xerostomia analysis (42 in the SPLS-IMRT group and 40 in the C-IMRT group). At 12 months post-IMRT, the incidence of xerostomia in the SPLS-IMRT group was significantly lower than that in the C-IMRT group (83.4% vs. 95.0%; P = 0.007), especially the grade 3 xerostomia (0% vs. 12.5%; P &lt; 0.001). However, the median change in XQ score (XQ change ) was similar between the two groups (11.9 points vs. 14.1 points; P = 0.194). Moreover, there was a significantly higher median fractional USFR (0.67 vs. 0.35; P = 0.024) and SSFR (0.66 vs. 0.32; P = 0.021) in the SPLS-IMRT group than the C-IMRT group. All 90 patients were included for survival analysis. With a median follow-up time of 37.8 months (IQR, 33.9–38.5 months), the 3-year locoregional relapse-free survival, distant metastasis-free survival, and overall survival in the SPLS-IMRT and C-IMRT groups were 92.5% vs. 90.9% (hazard ratio [HR], 1.84; P = 0.477), 83.8% vs. 81.7% (HR, 1.13; P = 0.816), and 88.9% vs. 88.2% (HR, 0.96; P = 0.949), respectively. Conclusions: SPLS-IMRT significantly reduced the incidence of xerostomia at 12 months post-IMRT in NPC by recovering parotid gland function earlier than C-IMRT, without compromising survivals. Phase III clinical trials are needed to confirm this result. Clinical trial information: NCT05020067.
Outcomes by tobacco history in E3311, a phase II trial of transoral surgery (TOS) followed by pathology-based adjuvant treatment in HPV-associated (HPV+) oropharynx cancer (OPC): A trial of the ECOG-ACRIN Cancer Research Group.
Authors: Ranee Mehra, Yael Flamand, Harry Quon, Joaquin J. Garcia, Gregory S. Weinstein, Umamaheswar Duvvuri, Bert W. O'Malley, Enver Ozer, Giovana R. Thomas, Wayne Koch, Neil D. Gross, Richard Bryan Bell, Nabil F. Saba, Miriam Lango, Rodrigo Bayon, Barbara Burtness, Robert L. Ferris
Journal: Journal of Clinical Oncology (2022)

6077 Background: E3311 is a phase II randomized study which showed favorable outcomes among intermediate (INT) risk HPV+ OPC patients (pts) who underwent TOS followed by pathology-guided or adapted, deintensified adjuvant treatment. Among HPV+ pts treated with definitive chemoradiation, survival outcomes are worse among those who smoked &gt; 10 pack years (pk-yrs). Methods: We retrospectively analyzed demographics, pathologic results, and efficacy outcomes from E3311 by smoking group (current (C) vs. former (F) and &gt; 10 vs. ≤10 pk-yrs  the latter a pre-specified stratification factor for INT patients). Binary and categorical variables were compared using a chi-square test (or Fishers exact test for small sample sizes). Ordinal variables were compared using a Wilcoxon rank sum test. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using a log-rank test. Results: Among 359 evaluable pts, performance status (PS) was significantly worse for pts with &gt; 10 pk-yrs vs. ≤10 pk-yrs (15.4% vs. 7.9% with PS of 1, p = 0.034). Primary site, margin status, histologic grade, stage, and extranodal extension were not significantly different between the groups of &gt; 10 vs. ≤10 pk-yrs. Smoking status (F vs. C) was available for 182 pts with a history of smoking. Slightly more C vs. F smokers had tonsil as primary site (79.5% vs. 65.0%, p = 0.09). Positive margins were significantly more frequent among C smokers (10.3% vs. 2.1%; p = 0.029). Overall, there were no significant differences in PFS (p = 0.55) or OS (p = 0.94), comparing those with &gt; 10 vs. ≤10 pk-yrs, or comparing C vs. F smokers (p = 0.76, p = 0.82, respectively). Similarly, no significant differences were observed within the treatment arms. (Table 1) Conclusions: In this analysis of smoking status in E3311, INT risk HPV+ OPC pts who are C smokers or have a history of &gt; 10 pk-yrs had favorable 3-yr PFS and OS rates that were not significantly worse than those with &lt; 10 pk-yrs history. This data represents the first treatment approach for HPV+ OPC in which outcomes were not influenced by smoking status. Clinical trial information: NCT01898494. [Table: see text]
Apatinib versus placebo in patients with locally advanced or metastatic, radioactive iodine-refractory, differentiated thyroid cancer: Post hoc analyses from the REALITY randomized clinical trial.
Authors: Yan-Song Lin, Shukui Qin, Zhiyong Li, Hui Yang, Wei Fu, Shaohua Li, Wenxin Chen, Zairong Gao, Weibing Miao, Huiqin Xu, Qing Zhang, Xinming Zhao, Jiandong Bao, Linfa Li, Yuan Ren, Chenghe Lin, Shanghua Jing, Qingjie Ma, Jun Liang, Guang Chen
Journal: Journal of Clinical Oncology (2022)

6095 Background: In the multicenter, double-blind, randomized, phase 3 REALITY study, apatinib significantly improved clinical benefits in terms of progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) compared to placebo with a tolerable safety profile in patients with progressive locally advanced or metastatic radioactive iodine-refractory, differentiated thyroid cancer (RAIR-DTC). Here, we investigate the association between baseline characteristics and survival endpoints. Methods: Post-hoc analyses of PFS and OS were done in patients treated with apatinib according to the following subgroups: ECOG performance status (PS) (0 vs 1-2), thyroglobulin (Tg) ( &lt; 223 vs ≥ 223 ng/mL), and tumor target lesions diameter ( &lt; 33.2 vs ≥ 33.2 cm). Results: Among 92 patients with RAIR-DTC included in the study, 46 patients received apatinib. As of December 3, 2021, median PFS was 25.77 (95% CI 11.14-not reached [NR]) vs 11.08 months (95% CI 7.17-NR) for ECOG PS 0 / 1-2, though no statistical significance (HR 0.454, 95% CI 0.161-1.285, p = 0.1373). The median OS was significant prolonged in patients with ECOG PS of 0 compared with those ECOG 1-2 (not reached vs 29.42 months, 95% CI 18.87-NR; HR 0.199, 95% CI 0.054-0.733, p = 0.0152). In subgroups by Tg, median PFS was 25.77 (95% CI 9.11-NR) vs 11.08 (95% CI 5.65-NR) months for Tg &lt; 223 / ≥ 223 ng/mL. A trend towards improved PFS was observed (HR 0.444, 95% CI 0.145-1.361, p = 0.1556). The median OS was significantly improved in patients with Tg &lt; 223 in contrast to those Tg ≥ 223 ng/mL (NR vs 25.87 months, 95% CI 13.58-NR; HR 0.151, 95% CI 0.033-0.689, p = 0. 0147). The median PFS for tumor target lesions diameter &lt; 33.2 cm was significantly improved relative to those ≥33.2 cm (25.77, 95% CI 11.14-NR vs 9.11 months, 95% CI 5.65-NR) with a significant difference (HR 0.289, 95% CI 0.097- 0.859, p = 0.0255); OS data in two subgroups were not mature (NR, 95% CI 29.42-NR vs NR, 95% CI 17.95-NR; HR 0.364, 95% CI 0.112-1.184, p = 0.0932). Conclusions: Post-hoc analysis indicated that among patients receiving apatinib, longer OS benefits were associated with better ECOG PS, lower Tg levels; longer PFS benefits were associated with smaller tumor diameter. These results suggest a better prognosis for early initiation of apatinib treatment in patients with RAIR-DTC. Clinical trial information: NCT03048877.
Feasibility and quality of life of postoperative concurrent radiotherapy and toripalimab in elderly patients with head and neck squamous cell carcinoma (IMPORT trial).
Authors: Ximei Zhang, Shengjin Dou, Lei Tao, Wen Jiang, Lulu Ye, Rongrong Li, Guopei Zhu
Journal: Journal of Clinical Oncology (2022)

6066 Background: For elderly patients with locally advanced head and neck squamous cell carcinoma (HNSCC), the role of postoperative concurrent chemotherapy was controversial since the intolerable toxicities and increased acute mortality, thus, radiotherapy alone was recommended. Aimed to seek out a feasible regimen for concurrent treatment, we evaluated the feasibility and quality of life of postoperative concurrent radiotherapy and toripalimab (anti-PD-1 antibody) in elderly HNSCC patients. Methods: The IMPORT trial was an investigator-initiated, multicentre, open-label, parallel-group, phase 2, randomized study. Patients were enrolled at 3 hospitals in China. We randomly assigned (1:1) patients aged＞65 years, with ECOG Performance Status(PS) of 0–2, and with postoperative Stage III-IV (AJCC 8th Staging system) HNSCC to concurrent radiotherapy (60-66Gy) and toripalimab (240mg on D0, D21 and D42)(RT+PD-1 group) or radiotherapy alone(RT group). Following stratification by PS(0-1 vs 2) and pathological adverse features (extranodal extension or positive margin vs others), patients were randomly assigned using a computer-generated randomization list. Acute toxicities were reported. Quality of life were evaluated by EORTC QLQ-C30 and QLQ-H&amp;N35 at baseline, week3, week6 and 1 month after radiotherapy, and the standard scores were compared between groups by linear mixed-effects models. Results: Between September 2020 and December 2021, 38 patients randomly assigned(19 per group). The median age were 70 years (range 66-81) for the RT+PD-1 group and 73 years (range 67-78 years) for RT group. 16 (84.2%) patients in the RT+PD-1 group and 15 (78.9%) patients in the RT group complete the planed radiation dose. In the RT+PD-1 group, 13 (68.4%) patients completed 3 cycles of toripalimab, 3 (15.8%) patients completed 2 cycles due to adverse events and 3 (15.8%) patients declined toripalimab; The most common adverse events of grade 3-5 was oral mucositis (55.6% vs 58.8%) and lymphocyte count decreased(61.1% and 41.2%) in RT+PD-1 group and RT group. In the RT+PD-1 group, only 1 patients experienced grade 3 immune-related enteritis. As to the quality of life scores evaluated by QLQ-C30, no difference was found in standard score of global health status, as well as in most functional scales including: physical, emotion, cognitive and social, except for role functioning (p = 0.045). As to the symptom scale scores evaluated by QLQ-H&amp;N35, no difference was found in standard score of pain, swallowing, dry mouth, opening mouth, and stick saliva, except for speech problem (p = 0.032). Conclusions: For elderly patients with locally advanced HNSCC, postoperative concurrent radiotherapy and toripalimab was safe and feasible. Concurrent toripalimab did not worsen quality of life scores in the majority of cases. Clinical trial information: NCT04523883.